Skip to main content

Enzyme-functionalized DNA nanostructures as tools for organizing and controlling enzymatic reactions

  • Guido Grossi (a1), Andreas Jaekel (a2), Ebbe Sloth Andersen (a3) and Barbara Saccà (a4)

Enzyme sequestration and compartmentalization are key factors in cell signaling and metabolism, evolved to solve the challenges of slow turnover rates, undesired pathway intermediates, and competing reactions. Inspired by nature, DNA nanoengineers have developed organizational systems to confine enzymes in two- and three-dimensional environments and to actuate them in response to precise external stimuli. DNA-scaffolded enzymes have applications for not only the in vitro reconstitution of proteins, peptides, and other molecular assemblies, but also to enable the generation of advanced functional nanomaterials for the development of, for example, fuel cells, biosensors, and drug delivery systems. Despite several challenges that still remain unsolved, the use of DNA scaffolds to arrange enzymes in space and time will help to realize biochemical nanofactories, where multiple components work together to produce novel and improved functional materials, rivaling the efficiency of biological systems.

Hide All
1. Kuchler, A., Yoshimoto, M., Luginbuhl, S., Mavelli, F., Walde, P., Nat. Nanotechnol. 11, 409 (2016).
2. Chen, A.H., Silver, P.A., Trends Cell Biol. 22, 662 (2012).
3. Simmel, F., Schulman, R., MRS Bull. 42 (12), 913 (2017).
4. Seeman, N.C., Nature 421, 427 (2003).
5. Rothemund, P.W.K., Nature 440, 297 (2006).
6. Gothelf, K., MRS Bull. 42 (12), 897 (2017).
7. Muller, J., Niemeyer, C.M., Biochem. Biophys. Res. Commun. 377, 62 (2008).
8. Conrado, R.J., Wu, G.C., Boock, J.T., Xu, H., Chen, S.Y., Lebar, T., Turnsek, J., Tomsic, N., Avbelj, M., Gaber, R., Koprivnjak, T., Mori, J., Glavnik, V., Vovk, I., Bencina, M., Hodnik, V., Anderluh, G., Dueber, J.E., Jerala, R., DeLisa, M.P., Nucleic Acids Res. 40, 1879 (2012).
9. Wilner, O.I., Shimron, S., Weizmann, Y., Wang, Z.G., Willner, I., Nano Lett. 9, 2040 (2009).
10. Liu, M., Fu, J., Hejesen, C., Yang, Y., Woodbury, N.W., Gothelf, K., Liu, Y., Yan, H., Nat. Commun. 4, 2127 (2013).
11. Zhou, C., Yang, Z., Liu, D., J. Am. Chem. Soc. 134, 1416 (2012).
12. Xin, L., Zhou, C., Yang, Z., Liu, D., Small 9, 3088 (2013).
13. Engelen, W., Janssen, B.M., Merkx, M., Chem. Commun. (Camb.) 52, 3598 (2016).
14. Endo, M., Katsuda, Y., Hidaka, K., Sugiyama, H., Angew. Chem. Int. Ed. Engl. 49, 9412 (2010).
15. Suzuki, Y., Endo, M., Katsuda, Y., Ou, K., Hidaka, K., Sugiyama, H., J. Am. Chem. Soc. 136, 211 (2014).
16. Suzuki, Y., Endo, M., Canas, C., Ayora, S., Alonso, J.C., Sugiyama, H., Takeyasu, K., Nucleic Acids Res. 42, 7421 (2014).
17. Kobayashi, Y., Misumi, O., Odahara, M., Ishibashi, K., Hirono, M., Hidaka, K., Endo, M., Sugiyama, H., Iwasaki, H., Kuroiwa, T., Shikanai, T., Nishimura, Y., Science 356, 631 (2017).
18. Chhabra, R., Sharma, J., Ke, Y., Liu, Y., Rinker, S., Lindsay, S., Yan, H., J. Am. Chem. Soc. 129, 10304 (2007).
19. Rinker, S., Ke, Y., Liu, Y., Chhabra, R., Yan, H., Nat. Nanotechnol. 3, 418 (2008).
20. Fu, J., Liu, M., Liu, Y., Woodbury, N.W., Yan, H., J. Am. Chem. Soc. 134, 5516 (2012).
21. Wilner, O.I., Weizmann, Y., Gill, R., Lioubashevski, O., Freeman, R., Willner, I., Nat. Nanotechnol. 4, 249 (2009).
22. Fu, J., Yang, Y.R., Johnson-Buck, A., Liu, M., Liu, Y., Walter, N.G., Woodbury, N.W., Yan, H., Nat. Nanotechnol. 9, 531 (2014).
23. Ke, G., Liu, M., Jiang, S., Qi, X., Yang, Y.R., Wootten, S., Zhang, F., Zhu, Z., Liu, Y., Yang, C.J., Yan, H., Angew. Chem. Int. Ed. Engl. 55, 7483 (2016).
24. Rasmussen, M., Abdellaoui, S., Minteer, S.D., Biosens. Bioelectron. 76, 91 (2016).
25. Van Nguyen, K., Giroud, F., Minteer, S.D., J. Electrochem. Soc. 161, H930 (2014).
26. Chen, J.H., Seeman, N.C., Nature 350, 631 (1991).
27. Banerjee, A., Bhatia, D., Saminathan, A., Chakraborty, S., Kar, S., Krishnan, Y., Angew. Chem. Int. Ed. Engl. 52, 6854 (2013).
28. Crawford, R., Erben, C.M., Periz, J., Hall, L.M., Brown, T., Turberfield, A.J., Kapanidis, A.N., Angew. Chem. Int. Ed. Engl. 52, 2284 (2013).
29. Andersen, E.S., Dong, M., Nielsen, M.M., Jahn, K., Subramani, R., Mamdouh, W., Golas, M.M., Sander, B., Stark, H., Oliveira, C.L., Pedersen, J.S., Birkedal, V., Besenbacher, F., Gothelf, K.V., Kjems, J., Nature 459, 73 (2009).
30. Kuzuya, A., Komiyama, M., Chem. Commun. (Camb.) 28, 4182 (2009).
31. Douglas, S.M., Bachelet, I., Church, G.M., Science 335, 831 (2012).
32. Perrault, S.D., Shih, W.M., ACS Nano 8, 5132 (2014).
33. Sprengel, A., Lill, P., Stegemann, P., Bravo-Rodriguez, K., Schoneweiss, E.C., Merdanovic, M., Gudnason, D., Aznauryan, M., Gamrad, L., Barcikowski, S., Sanchez-Garcia, E., Birkedal, V., Gatsogiannis, C., Ehrmann, M., Sacca, B., Nat. Commun. 8, 14472 (2017).
34. Linko, V., Eerikainen, M., Kostiainen, M.A., Chem. Commun. (Camb.) 51, 5351 (2015).
35. Douglas, A.J., Young, J.A., Nature 393, 152 (1998).
36. Nomura, S.M., Tsumoto, K., Hamada, T., Akiyoshi, K., Nakatani, Y., Yoshikawa, K., Chembiochem 4, 1172 (2003).
37. Zhu, T.F., Szostak, J.W., J. Am. Chem. Soc. 131, 5705 (2009).
38. Zhao, Z., Fu, J., Dhakal, S., Johnson-Buck, A., Liu, M., Zhang, T., Woodbury, N.W., Liu, Y., Walter, N.G., Yan, H., Nat. Commun. 7, 10619 (2016).
39. Gray, M.J., Wholey, W.-Y., Wagner, N.O., Cremers, C.M., Mueller-Schickert, A., Hock, N.T., Krieger, A.G., Smith, E.M., Bender, R.A., Bardwell, J.C.A., Jakob, U., Mol. Cell 53, 689 (2014).
40. Zhang, Y., Tsitkov, S., Hess, H., Nat. Commun. 7, 13982 (2016).
41. Gao, Y.N., Roberts, C.C., Zhu, J., Lin, J.L., Chang, C.E.A., Wheeldon, I., ACS Catal. 5, 2149 (2015).
42. Lin, J.L., Wheeldon, I., ACS Catal. 3, 560 (2013).
43. Glettenberg, M., Niemeyer, C.M., Bioconjug. Chem. 20, 969 (2009).
44. Rudiuk, S., Venancio-Marques, A., Baigl, D., Angew. Chem. Int. Ed. Engl. 51, 12694 (2012).
45. Timm, C., Niemeyer, C.M., Angew. Chem. Int. Ed. Engl. 54, 6745 (2015).
46. Grossi, G., Jepsen, M.D.E., Kjems, J., Andersen, E.S., Nat. Commun. 8, 992 (2017).
47. Freeman, R., Sharon, E., Tel-Vered, R., Willner, I., J. Am. Chem. Soc. 131, 5028 (2009).
48. Freeman, R., Sharon, E., Teller, C., Willner, I., Chem. Eur. J. 16, 3690 (2010).
49. Cassinelli, V., Oberleitner, B., Sobotta, J., Nickels, P., Grossi, G., Kempter, S., Frischmuth, T., Liedl, T., Manetto, A., Angew. Chem. Int. Ed. Engl. 54, 7795 (2015).
50. Rajendran, A., Endo, M., Katsuda, Y., Hidaka, K., Sugiyama, H., J. Am. Chem. Soc. 133, 14488 (2011).
51. Benson, E., Mohammed, A., Gardell, J., Masich, S., Czeizler, E., Orponen, P., Hogberg, B., Nature 523, 441 (2015).
52. Zhang, F., Jiang, S., Wu, S., Li, Y., Mao, C., Liu, Y., Yan, H., Nat. Nanotechnol. 10, 779 (2015).
53. Veneziano, R., Ratanalert, S., Zhang, K., Zhang, F., Yan, H., Chiu, W., Bathe, M., Science 352, 1534 (2016).
54. Mikkila, J., Eskelinen, A.P., Niemela, E.H., Linko, V., Frilander, M.J., Torma, P., Kostiainen, M.A., Nano Lett. 14, 2196 (2014).
55. Rodrigues, R.C., Ortiz, C., Berenguer-Murcia, A., Torres, R., Fernandez-Lafuente, R., Chem. Soc. Rev. 42, 6290 (2013).
56. Geng, C., Paukstelis, P.J., J. Am. Chem. Soc. 136, 7817 (2014).
57. Raushel, F.M., Thoden, J.B., Holden, H.M., Acc. Chem. Res. 36, 539 (2003).
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

MRS Bulletin
  • ISSN: 0883-7694
  • EISSN: 1938-1425
  • URL: /core/journals/mrs-bulletin
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed